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Title: Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology

Journal Article · · Immunological Reviews
DOI:https://doi.org/10.1111/imr.12671· OSTI ID:1543993
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [4]; ORCiD logo [1]; ORCiD logo [2]
  1. Univ. of Michigan, Ann Arbor, MI (United States)
  2. Univ. of Michigan Medical School, Ann Arbor, MI (United States)
  3. Univ. of Michigan, Ann Arbor, MI (United States); Univ. of Michigan Medical School, Ann Arbor, MI (United States)
  4. Univ. of Pittsburgh, PA (United States)

Abstract Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long‐term control of infection while also preventing an over‐zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro‐ and anti‐inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host‐directed therapies.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE Office of Science (SC)
OSTI ID:
1543993
Alternate ID(s):
OSTI ID: 1471137
Journal Information:
Immunological Reviews, Vol. 285, Issue 1; ISSN 0105-2896
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 116 works
Citation information provided by
Web of Science

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IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early Mycobacterium tuberculosis Infection journal December 2019
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Inhibition of interferon-γ production and T-bet expression by menthol treatment of human peripheral blood mononuclear cells journal March 2019
The Role of Dimensionality in Understanding Granuloma Formation journal November 2018
Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation journal February 2020
Introduction to modeling viral infections and immunity journal August 2018
The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment journal February 2020
The Association between Inflammatory Biomarkers and Cardiovascular Autonomic Dysfunction after Bacterial Infection journal March 2022

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